Influence of maternal cytokines during pregnancy on effector and regulatory T helper cells as etiological factors in autism

City:

Newark

State/Province:

NJ

State/Province Full:

New Jersey

Country:

United States

Despite the specific genes or environmental exposures which may contribute to ASD, one theme that emerges from clinical and experimental studies is inflammation and autoimmunity in individuals with ASD and their families. Such an immune response may be the consequence of genetic and environmental interactions leading to pathophysiology and symptomatology of the disorder. In order to better study the immune response, Dr. Ponzio and his colleagues propose to use well-documented experimental models of ASD to test the hypothesis that stimulation of the maternal immune system during pregnancy alters the normal proportions of newly discovered populations of lymphocytes known as T Helper 17 (TH17) cells and T regulatory (Treg) cells, the balance of which may be responsible for determining whether or not the observed neuroinflammation in ASD occurs. Activation of specific types of lymphocytes during an immune response causes secretion of proteins (known as cytokines) that can induce inflammation. If this occurs during pregnancy, these cytokines may cross the placenta, enter the fetus, and influence neural development and cause immunological outcomes and ASD-like behavior patters in the offspring. This experiment will examine different mechanisms by which cytokine secretions may mediate neural development, including whether or not they alter the placenta, whether they can enter fetal tissues, and if they promote differentiation of immune cells which alter the neuroinflammatory process. What this means for people with autism: A better definition of the induction and function of Th17 and T regulatory (Treg) cells is critical in understanding the pathogenesis and regulation of inflammatory disorders and autoimmunity and will elucidate immunological mechanisms that may be triggered by environmental factors that promote the development and pathogenesis of ASD.